Rationale for Antimicrobial Combinations

Rationale for Antimicrobial Combinations

1. Definition & scope of the problem

• Antimicrobial combination therapy = the concurrent administration of more than one antimicrobial agent (AMA) to a single patient for a single infectious indication; it is justified only with a specific purpose and "not blindly in the hope that if one is good, two should be better and three should cure almost any infection." (KDT 8e Ch.50, p.749)
• The default position is monotherapy: "For definitive therapy, combination antibiotic therapy is an exception, rather than a rule. Once a pathogen has been isolated, monotherapy is preferred unless compelling data exist in favor of combination therapy." (G&G 14e Ch.56, p.1129)
• Using multiple antibiotics where a single agent would suffice increases toxicity and inflicts unnecessary damage on the patient's protective fungal and bacterial flora; combinations are therefore reserved for defined "special circumstances." (G&G 14e Ch.56, p.1129)
• This topic concerns the rationale (indications), mechanisms of synergy, prevention of resistance, disadvantages, and in-vitro testing of antimicrobial combinations — not fixed-dose combinations generically, and not the molecular mechanisms of antimicrobial resistance per se (those are covered separately). (scope per topic brief)